Neuroprotective strategies hold significant promise for helping survivors of non-Hodgkin’s lymphoma (NHL) by addressing the neurological complications that often arise from both the disease itself and its treatments. NHL survivors frequently face cognitive impairments, peripheral neuropathy, and other neurophysiological dysfunctions caused by tumor effects, systemic inflammation, metabolic disturbances, and neurotoxic cancer therapies such as chemotherapy and radiotherapy. These neurological challenges can severely impact quality of life, daily functioning, and long-term health outcomes.
The neurological problems in NHL survivors stem from multiple overlapping mechanisms. Tumors can directly infiltrate nervous tissue or trigger paraneoplastic syndromes, where the immune system mistakenly attacks the nervous system. Additionally, systemic inflammation driven by cytokines like interleukin-6 and tumor necrosis factor-alpha contributes to neural damage. Treatments, while life-saving, often induce neurotoxicity that disrupts brain structure, connectivity, and neurogenesis, particularly in regions like the hippocampus that are critical for memory and learning. This results in symptoms commonly referred to as “chemo brain,” including difficulties with attention, memory, processing speed, and executive function.
Neuroprotective strategies aim to prevent or mitigate these neurological effects through a combination of pharmacological and non-pharmacological approaches. Pharmacological agents such as amifostine have been explored for their ability to shield neural tissue from chemotherapy-induced damage. However, no universally effective drug treatment for cognitive impairment post-chemotherapy currently exists, highlighting the need for complementary interventions.
Non-pharmacological interventions play a crucial role in supporting neurological health in NHL survivors. Techniques like massage therapy, aromatherapy, mindfulness, guided imagery, music and art therapy, and sleep optimization have demonstrated benefits by modulating neuroimmune pathways, reducing inflammation, and enhancing neuroendocrine balance. For example, massage therapy can lower cortisol and pro-inflammatory cytokines while increasing serotonin and oxytocin, which collectively reduce pain and stress. Mindfulness and guided imagery influence brain regions involved in emotion regulation and gene expression, decreasing inflammatory signaling and promoting cellular resilience. These interventions are generally safe but require individualized assessment to avoid risks, especially in medically fragile cancer survivors.
Lifestyle factors also contribute significantly to neuroprotection. Regular physical exercise has been shown to improve cognitive functions such as executive control, processing speed, and concentration by promoting neurogenesis, enhancing cerebral blood flow, and reducing oxidative stress. Nutritional strategies rich in antioxidants and polyphenols support neuronal resilience and may suppress tumorigenesis, further aiding brain health. Emerging evidence suggests that probiotics might reduce chemotherapy-related cognitive impairment by modulating gut-brain axis interactions, although more research is needed.
Advanced diagnostic tools including functional MRI, electroencephalography, and biomarker profiling (e.g., neurofilament light chain levels) enable early detection of neurological dysfunction and help tailor neuroprotective interventions. Personalized neuro-oncological care integrates these diagnostics with cognitive rehabilitation and non-invasive neuromodulation techniques such as transcranial magnetic stimulation and transcranial direct current stimulation. These approaches aim to restore neural connectivity and improve cognitive outcomes.
A multidisciplinary approach is essential for effective neuroprotection in NHL survivors. Collaboration among oncologists, neurologists, neuropsychologists, rehabilitation specialists, and nutritionists ensures comprehensive care that addresses the complex interplay of cancer, treatment effects, and neurological health. Routine cognitive and neurological screening should be standard practice to identify impairments early and implement timely interventions.
While some chemotherapy-induced cognitive impairments improve within one to five years after treatment, certain deficits, especially in verbal fluency and psychomotor speed, may persist longer or become permanent. Neuroprotective strategies that combine pharmacological agents, lifestyle modifications, cognitive training, and supportive therapies offer the best chance to enhance recovery and maintain quality of life.
Future research priorities include large-scale longitudinal studies to map the trajectory of neurological recovery, randomized controlled trials to evaluate emerging neuroprotective treatment
